The proposed work is organized into two main sections. 1) Cornea. The role of the bounding membranes, the epithelium and endothelium, in the maintenance of corneal thickness will be investigated using various drugs to either stimulate or inhibit fluid movement across the membranes. In addition, the effects of metabolic inhibitors on corneal thickness regulatory systems will be examined in detail to determine the underlying mechanisms of hydration control. Various drugs will be assessed in terms of ocular tissue penetration for the efficacy of different vehicles in drug deliveries to the eye. 2) Aqueous humor dynamics. The characteristics of the ciliary epithelium in the living animal will be determined by analysis of aqueous humor: plasma ratios in the living animal and ranges for various parameters obtained from a mathematical analysis of the data. Mathematical formulations will also be applied to data obtained in man where sufficient data is available to allow the determination of secretory rate and ultrafiltration. In experimental animals the effects of drugs on the outflow pathways aqueous humor from the eye will be examined using tracers in association with a freeze drying technique which allows the use of water soluble tracers. BIBLIOGRAPHIC REFERENCES: Green, K. and Kim, K. 1976. Interaction of adrenergic blocking agents with prostaglandin E2 and tetrahydrocannabinol in the eye. Invest. Ophthalmol. 15, 102-112. Green, K. and Bowman, K. 1976. Effect of marihuana derivatives on intraocular pressure in the rabbit. In, The Pharmacology of Marihuana, eds. M.C. Braude and S. Szara, Raven Press. pp. 803-813.